Study summary:

Several studies have demonstrated that therapeutic agents used to reduce glucose levels
and/or weight can delay the onset of type 2 diabetes. Intriguingly, angiotensin converting
enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) also result in reduction in
the onset of type 2 DM. The most striking effect was found with Ramipril in the HOPE study.
The onset of new type 2 DM was reduced by 34% (p<0.001) as compared to placebo. Furthermore,
the results of the DREAM trial demonstrate that Ramipril at a dose of 15 mg can
significantly reverse impaired glucose tolerance. However, the mechanisms underlying
Ramipril effects to delay type 2 diabetes are not known.
The proposal will be focused on determining the integrated in-vivo mechanisms responsible
for Ramipril's effects on delaying type 2 DM and restoring normal glycemia in patients with
impaired glucose tolerance.
The specific aims of the project are:
- to determine the effect of Ramipril on insulin resistance at the level of the liver and
peripheral tissues,
- to determine the effect of Ramipril on endothelial function,
- to determine the effects of Ramipril on insulin secretion, and
- to determine the effects of Ramipril on substrate flux, lipolysis and inflammatory
cytokines.